Acquired Brain Injury & Neurodegenerative Diseases

Question 1

Name all types of memory.

Answer 1

Sensory memory. 
STM. 
LTM - explicit + implicit. 
Explicit (declarative) - episodic + semantics. 
Implicit - procedural.

Question 2

What type of amnesia did Henry Molaison have and what evidence did his case provide?

Answer 2

Anterograde amnesia. Events taking place after surgery were never remembered.
Affected - declarative.
Not affected - working memory, procedural, old declarative.
Lesion of the hippocampus - hippocampal regions are critical for forming new memories.

Question 3

What is a weakness of studying amnesic patients?

Answer 3

Damage never limited to one structure.
Lesions are always different.
E.g. HM’s lesion included much of the medial temporal lobe..

Question 4

What did lesion studies into monkeys show when testing for recognition memory?

Answer 4

Task - delayed non-match to sample.
Recognition memory tested.
When both the hippo + Rhinal cortex were lesioned; there was severe impairment. When only one was lesioned - mind impairment.
There was no impairment with a short delay - memory not visual impairment.

Question 5

What is the rhinal cortex?

Answer 5

Main input pathway to the hippo.
Highly processed sensory data from cortical association areas pass through RC to hippo. Gateway for convergence of uni and multi-modal sensory input to hippo.

Question 6

Why is the hippocampus hard to study?

Answer 6

High level brain area. Response are very complex.

Question 7

What are place cells in the hippocampus?

Answer 7

These cells fire when the animal is in a specific region of space.
Cells tile the environment to provide a spatial map.
Evidence: hippo lesions impair spatial navigation.

Question 8

What is the evidence for hippocampal place cells in humans?

Answer 8

London taxi driver study.
Larger posterior hippocampus - the more experience; the larger the posterior hippo.
Not seen for bus drivers.

Epilepsy patients. Place-responsive cells active during virtual navigation. Same cells activated during subsequent recall. Occurred without actual navigation, therefore, hippo provides spatial context for memories.

Question 9

What does hippocampal damage tell us about memory?

Answer 9

Dissociable systems.
Role of hippo goes beyond spatial memory (e.g. HM - no new declarative memories). More general role in linking memories to where!
Crucial in forming new memories but not for recall of older memories.
Anterograde amnesia. Memories must be consolidated and
hippo-independent overtime!!!

Question 10

What is Korsakoff’s syndrome cause by?

Answer 10

Thiamine deficiency due to alcoholism.

Question 11

What damage is caused in the Korsakoff’s syndrome?

Answer 11

Generalised cortical atrophy.
Major damage to diencephalon (thalamus + mammillary bodies - relay between hippo and cortex).
Damage means hippo cannot output to cortex.
Severe anterograde + retrograde.

Question 12

What evidence has Korsakoff’s syndrome provided?

Answer 12

Temporal gradient in retrograde amnesia - earlier memories better preserved.
Overtime, memories become hippo-independent (takes a long time).

Question 13

How does consolidation of memories occur?

Answer 13

1. Sensory info processed in hippo formation + integrated or bound as a memory episode.
2. Recall - activation of cortex by hippo via mammillary bodies + thalamus.
3. Hippo teaches cortex memory trace.
4. Memories become consolidated + independent of thalamus and hippo.

Question 14

What is a competing view of how consolidation of memories could occur?

Answer 14

Episodic memories more semantic over time and represented in cortex as meaning.

Question 15

How do semantic memories work without a hippo?

Answer 15

Patients with large lesions of hippo. Given tests of semantic knowledge.
Earlier knowledge recall was intact. Some capacity for new learning (below control levels).
Suggests cortical structures can support limited semantic learning without hippo!

Question 16

What are the two main types of strokes?

Answer 16

Ischemic - strokes affect oxygen supply to brain; thrombotic + embolic stroke.
Haemorrhagic stroke - rupture of blood vessels.
Results in: functional disturbance of surrounding neurons, primary cell death (apoptosis), secondary cell death. Lesion growth continues after injury - degenerative + restorative processes. Brain is plastic + can reorganise itself to consolidate recovery.

Question 17

How well do motor functions recover during rehabilitation?

Answer 17

Recovery over first 3 months.

Motor function can recover nearly completely.

Question 18

How well do cognitive function recover during rehabilitation?

Answer 18

Impairment in psychomotor speed + executive function.
6 months - recovery is possible in executive function + visual memory.
After 6 months - little improvement.

Question 19

What is aphasia?

Answer 19

Consequence of stroke.
Damage to LH in frontal/temporal regions.
Problems producing speech.

Question 20

What is agraphia?

Answer 20

Damage to LH visual areas involved in writing.

Spelling + writing issues.

Question 21

What is alexia?

Answer 21

Damage to visual/temporal regions in LH.

Problems reading.

Question 22

Explain the dual-route theory of reading in alexia.

Answer 22

Coltheart.
Dorsal phonological route connects the visual-parietal-frontal areas. Used for phonetically decoding words.
Ventral route connects visual to semantic areas in the temporal lobe. Direct mapping of words onto meaning.
Some patients can’t read non-words + recognise rhymes - dorsal route impaired. Good reading ability. Better at concrete than abstract words (imageability effect). Poor at reading function words.
Patients have to read via meaning using ventral route. OR!!! Reliance on RH. RH unable to perform letter-sound conversion. RH semantics imprecise leading to semantic errors.

Question 23

What is dementia?

Answer 23

Loss of cognitive functioning that affects daily life and activities.

Question 24

Name the main types of dementia.

Answer 24

Alzheimer’s, vascular, Lewy body, frontotemporal, posterior cortical atrophy.

Question 25

Explain the main Alzheimer’s symptoms.

Answer 25

Progressing disease.
Initial symptoms in memory domain. Worsen over time.
Later stages - mood + behavioural disturbances, loss of independence.
Cognitive impairment phase.
Age biggest risk factor.
Early onset familial Alzheimer’s disease - clear inheritance pattern. Minority of cases (1%). Helps to identify specific genes responsible.

Question 26

What diagnoses indicates a high risk go transition to AD?

Answer 26

Mild cognitive impairment.

Criteria - evidence of impairment in 1+ cognitive domains, daily function not impaired.

Question 27

What are the current AD treatment options?

Answer 27

Cholinesterase inhibitors - increase ACh levels in brain.
ACh - role in learning + memory.
Each broken down by acetylcholinesterase in synapse. By blocking this enzyme - AChE inhibitors increase ACh.

Question 28

What are the three major AD theories?

Answer 28

Cholinergic, amyloid, tau.

Question 29

Why has no new drug for Alzheimer’s been developed in 20 years?

Answer 29

Lack of understanding to what causes AD.

Question 30

Explain the cholinergic hypothesis.

Answer 30

Post-mortem studies.
Reduced levels of enzyme responsible for synthesis of ACh in cortex of AD patients. Loss of cholinergic neurons in basal forebrain. Detectable at preclinical stages + advances as disease progresses.

Question 31

What is a negative of AChEIs for AD treatment?

Answer 31

Improve symptoms in 50% of cases. Improvements sustained for 2 years.
Drugs are no disease modifying. Not all patients respond.

Question 32

Why is the cholinergic hypothesis no longer favoured?

Answer 32

ACh is not only NT system affects in AD.

Other pathology?

Question 33

What are the two main neural markers for AD?

Answer 33

Amyloid-beta plaques.

Neurofibrillary tangles.

Question 34

What is amyloid-beta + its role in AD?

Answer 34

Fragment of a larger protein called APP.
In AD, abnormal cleavage of APP = higher levels of amyloid beta 40 + 42.
42 is insoluble + clumps into toxic plaques.

Question 35

What genes does familial AD implicate?

Answer 35

Genes involved in the production of amyloid beta.

Question 36

What are neurofibrillary tangles+ its role in AD?

Answer 36

Tau protein stabilises the microtubules which transport nutrients + molecules from cell body to axon to dendrites.
In AD, abnormal chemical changes affect tau. Becomes hyperphophorylated + forms neurofibrillary tangles which impair microtubule function.

Question 37

How do you measure in amyloid?

Answer 37

PET uses a radioactive tracer injected into vein. More expensive and less safe than MRI.
11C-PIB tracer binds to AB plaques - higher binding in AD patients.
Amyloid levels predict progression from MCI to AD.

Question 38

How do amyloid plaques progress in AD?

Answer 38

Post-mortem + PET.

Begin in hippo then temporal + frontal lobe. Eventually affects entire cortex.

Question 39

How does tau progress in AD?

Answer 39

Same as amyloid but later on.

Question 40

What is the amyloid cascade hypothesis?

Answer 40

Plaques detected very early on.

Deposition of beta-amyloid is the imitating event in AD which trigger symptoms an other pathology.

Question 41

What is the first strategy for anti-amyloid drugs?

Answer 41

Block/inhibit the overproduction of AB. Inhibit enzymes which breakdown APP into AB. Gamma secretase inhibitors; beta secretase inhibitors.
Use semagaestat; but leads to significant negative effects on cognition!

Question 42

What is the second strategy for anti-amyloid drugs?

Answer 42

Promote clearance. Active immunisation or passive immunisation.

Question 43

Explain active immunisation in the secondary strategy.

Answer 43

Induce a immune response to clear AB.

AN 1792 - reduced AB levels but no effect on symptom progression. Severe side effects.

Question 44

Explain passive immunisation in the secondary strategy.

Answer 44

Use antibodies which directly clear AB.
Solanezumab.
But still no effect on symptom progression.

Question 45

What is a negative of drug treatments based on the amyloid hypothesis?

Answer 45

They have all failed so far.
All trials were on patients.. Perhaps need to focus on amyloid removal earlier in life OR target tau?
30% of controls show high levels of amyloid… Also amyloid load doesn’t correlate with symptoms in AD. Tau correlates better!

Question 46

What drugs are currently in development?

Answer 46

Drugs to reduce tau.
Preventative strategies may be better?
Targeting risk factors (e.g. smoking).
Still no treatment for AD.

Question 47

What is vascular (multi-infarct) dementia and what are its symptoms?

Answer 47

Loss of cognitive functioning due to series of silent strokes.
Symptoms: progressive cognitive impairment after each stroke.
Improvement between strokes possible.
High blood pressure, diabetes - risk factors.
Early detection is essential - treatment involves targeting risk factors. Diagnosis difficult.

Question 48

What is dementia with Lewy Bodies and what are its symptoms?

Answer 48

Lewy bodies = abnormal clumps of protein that develop inside cells. Lead to cell death.
Shares symptoms of Alzheimer’s + Parkinson’s.
Frequently misdiagnosed.
Lewy Bodies contribute to PDD in which movement disorder progresses into dementia.

Question 49

What is frontotemporal dementia and what are its symptoms?

Answer 49

Different pathology to Alzheimer’s. No amyloid or neurofibrillary tangles.
Pick bodies inside cells (clumps of tau protein).
Symptoms: impaired planning, judgment, language symptoms.
Frontal variant - frontal lobe atrophy.
Semantic dementia - anterior temporal lobes atrophy.

Question 50

What is posterior cortical atrophy and what are its symptoms?

Answer 50

Atypical variant of Alzheimer’s. Similar pathology.
Posterior parietal cortex.
Symptoms: blurred vision, agnosia, impaired spatial skills, reading + writing.
Memory + spoken language preserved until late stages.